The present invention relates in general to computer systems and databases for managing product data. More particularly, the invention employs computer systems and proprietary databases for gathering, storing, processing and distributing new adverse event data associated with medical and non-medical products, including drugs, medicaments, biologicals, food additives, chemicals and the like, or devices, as well as computer databases for generating, storing, analyzing and processing information related thereto.
For several reasons, adverse events associated with medical and non-medical products are greatly understated. As a matter of cost, thorough safety studies are typically very expensive to conduct. In the field of generic pharmaceuticals, for example, the cost of doing safety testing is prohibitive because a manufacturer""s survival in the business is based on being a low cost producer. By the time a product becomes generic, safety information relating to the drug has already been generated and shared. Thus, a manufacturer of a generic drug enjoys the benefits of the information without incurring the cost of the original safety studies, and there is no legal or economic motivation to conduct additional studies after a drug goes off patent.
Manufacturers also have little incentive to identify adverse events related to their products. As the number and/or types of identified adverse event increases with respect to a particular product, the product becomes less attractive to consumers and the manufacturer""s exposure to potential product liability litigation increases.
The safety studies necessary for medical and/or related products, such as drugs, biologicals, medical devices and cosmetics, to receive marketing approval generally involve relatively small populations of individuals (typically a few hundred to a few thousand, or less), who are observed for relatively short periods of time in prospective randomized studies. The studies generally involve strict inclusion criteria, thus persons in the study often differ in many respects from those individuals who actually use the drug post-marketing. The differences between the safety studies participants and the post-marketing consumers may include age, sex, race, preexisting medical conditions, and use of other drugs or devices. Pre-marketing safety studies are, therefore, a less than desirable means of identifying the full array of potentially adverse product events that may occur in populations of general and specific post-marketing consumers.
Post-marketing safety studies normally involve the voluntary reporting of potential adverse events. However, there is often no way to be certain that all occurrences are reported or, in fact, whether each reported event was caused by the medical product or not. For instance, adverse events generally are reported if they occur within a short time of initiating treatment with a product. Thus, it is difficult for a clinician to link an adverse event to a medical product if the event occurs months or years after it was first prescribed, or even after use of the product was discontinued.
Additionally, when a potential adverse event is something that also frequently occurs in people who have not used the medical product, it is difficult to determine if the medical product may have increased the frequency and/or magnitude of the event. This scenario is problematic because the incidence of such events in a matched control population is often not known. Thus, under normal safety testing conditions, it cannot be readily discerned whether the incidence of adverse events is greater in the group using the medical product versus a corresponding control population. Consequently, since the rate or intensity of an adverse event associated with the use of a product cannot be accurately determined, a reliable assessment cannot be made of whether the risk of using a product exceeds its benefit.
Pre-marketing and post-marketing of medical products is regulated by the Food and Drug Administration (FDA), and manufacturers are required to disclose all adverse events caused by their products. Nevertheless, in the pharmaceutical industry very few, truly comprehensive and detailed studies on adverse events are conducted. Most of the studies are performed by contract research organizations, funded by pharmaceutical companies as part of the FDA-required evaluation. A few government-funded studies may also be performed. However, in general, neither of these sorts of studies detect the frequency of adverse events in specific subgroups, such as those defined by typical demographic factors, e.g., age, race, sex, etc.
Moreover, the data from each manufacturer""s study into the potential adverse events resulting from the use of a product is made free to the public, including to competing product manufacturers, and to the FDA. However, because the data is limited, it has in some instances been misused, and sectors of the pharmaceutical industry remain underdeveloped. In other words, some products continue to be prescribed, when they should not be, while other products are not prescribed, when they should be. The result in either case, may be the occurrence of unnecessary adverse events and patient suffering. Accordingly, consumer costs for improperly prescribed medical products is needlessly high, since a manufacturer""s cost to produce a medical product, which is passed on to the consumer, includes not only actual manufacturing costs, but also any costs arising from the occurrence of adverse events. For example, some vaccine manufacturers are responsible for compensating individuals who develop unforeseen adverse responses to the vaccine.
Most manufacturers or distributors of products or devices are required by law to warn consumers about potential adverse events, even though this information is generally inadequate as described above. With prescription pharmaceuticals, this information is called xe2x80x9clabeling,xe2x80x9d and is generally included in a xe2x80x9cpackage insert.xe2x80x9d With industrial chemicals, there is often a xe2x80x9cmaterial safety data sheet,xe2x80x9d also called a xe2x80x9cproduct safety data sheet.xe2x80x9d Consumer products including foods with chemical additives, over the counter medicines, electronic instruments, machinery or chemicals the information may be inserted in a piece of paper or written on a outer container, such as a cardboard box, or on an inner container, such as a plastic, paper or foil container which holds the drug or medicament. However, the location of the safety information may vary with the product and or industry.
One skilled in the art will know where and how the safety information, is or can be provided by the company manufacturing or selling the product or device. This information can also be termed a xe2x80x9csafety data sheet,xe2x80x9d as a generic term describing safety information included with any type of product or device.
By comparison, proper product labeling discourages those at high risk for an adverse response from utilizing the product, thus decreasing adverse events and, ultimately, the consumer cost of the product. Some factors affecting high-risk use include drug dosing and adverse drug combinations. If consumers are placed on notice through proper labeling, which describes the potential for the occurrence of an adverse event associated with dosage, drug interactions, preexisting conditions and other high risk factors, the number of adverse events is significantly reduced. This decreases the manufacturer""s product liability exposure, which ultimately reduces product cost to the consumer. To date, however, there has been no realization of the potential for comprehensive, subscriber-accessible proprietary product safety information, such as a database, to enhance the quality and reliability of adverse event reporting and product labeling.
U.S. Pat. Nos. 5,737,539; 5,833,599; 5,845,255; and 5,908,383 disclose computerized systems for providing patient-specific medical treatment information. The systems enable health care providers, such as medical doctors, to access databases containing pharmacological or other medical information via a computer, and to match a patient""s medical symptoms and/or prescription history with known data to produce an appropriate prescription or treatment for the patient. These systems, however, do not analyze raw adverse event data or create proprietary adverse event information based on such data that may be used to identify new uses or restrictions for medical products, or to develop improved packaging or labeling information that accompanies a medical product.
Pharmacoepidemiology is a scientific field pertaining to the analysis of data to test or confirm a specific hypothesis pertaining to an adverse event, and to the utility of a pharmaceutical product. The field has not been utilized in the past for the commercial purpose of generating purified data for the purpose of developing proprietary new uses and kits, wherein the data pertains to discovering previously undetermined adverse events resulting from the use of a product. Pharmacoepidemiology can be performed by analyzing medical records, health care records, such as drug sales or billing information, or by conducting specific surveys based upon relevant questions. Medical records can be reviewed using a computer if the records are in a computer readable form.
Pharmacoepidemiology is a field principally involved in hypothesis testing. It is not designed to commercially develop proprietary new uses for new or existing products. For example, an adverse event may be independently reported by more than a dozen physicians, at which point a group of researchers may perform an epidemiological study to confirm an association among the reports. However, the results are often held in doubt until a second group of researchers performs a study to confirm the findings in the first research report. Sometimes pharmaceutical companies sponsor pharmacoepidemiological studies. However these are usually only performed because a regulatory agency, such as the FDA, has requested the information, after it has received reports of possible adverse events.
After several such studies are performed, a pharmaceutical company may include the results in a package insert. The adverse event information is not, and can not be made proprietary, since the findings are made obvious after one or more physician report the association, and act upon the finding. Confirming the findings by conducting pharmacoepidemiological studies, however simply increases the proportion of users who utilize the safer use, it does not create new uses.
Computerized pharmacoepidemiological studies are performed more frequently in hospital-based settings, in which case all of the pertinent data is likely to be linked by a computer. For example, in such a setting, the laboratory, radiology, discharge reports, and billing statements may all be networked and accessed by computer. Epidemiological studies by computer on outpatients are more difficult to perform, since there are few places where all of the pertinent information is on a computerized system. Medical insurance records may be the most likely the single greatest source of patient information.
However, the process of searching databases in attempt to discover new adverse events has been frowned upon as unreliable. For one reason, based upon current statistical methods, one in every 20 associations that reach statistical significance (xcfx81=0.05) are merely do to chance, alone. Furthermore, a statistically significant association, even if it is not due to chance, is still unable to provide a causal relationship. Confounding variables explain many associations between a product and an adverse event.
In addition to studies conducted by Kaiser and Group Health, extensive computerized pharmacoepidemiology has been performed by groups at the University of Utah (Classen et al., N. Engl. J. Med. 326(5):281-6 (1992)), at Harvard University (Brewer et al., JAMA 281(9):824-9(1999)), two or more groups in the United Kingdom (Mackay, Drug Saf. 19(5):343-53(1998)), and a few others. None has attempted to purify/transform adverse event information into new adverse event information for the development of proprietary new uses or proprietary kits.
As described by Chen et al. (Pediatrics 99(6) (1997)), computers have also been used to verify previously reported adverse events related to vaccines. The VSD project discussed therein promotes utilizing its research in the development and use of safer vaccines. However, it does not disclose the notion of identifying new and proprietary uses for existing vaccines based on the discovery of new adverse events associated with the vaccines. Moreover, the VSD project was unable to discern new adverse events from previously reported adverse events.
Little if any use for adverse event information is taught in the prior art. Classen (U.S. Pat. No. 5,728,385) discloses new methods for administering vaccines, which involved timing of the immunization. The new improved use which related to changes in the timing of dosing, was not directly related to an adverse event but was an new efficacy use, i.e., improvement when given earlier. The improvement, i.e., prevention of a chronic immune mediated disorder was limited to immune stimulants (vaccines) and pertained to autoimmune diseases, allergies, and immune mediated cancers. Furthermore, the ""385 patent provided a more efficacious use of the vaccine, i.e., improved protection when the vaccine was administered earlier, and the relevance of age at the time of immunization. Furthermore the analysis in humans did not involve databases where the outcome, chronic immune mediated disorders, were linked to immunization records, nor did it describe screening or determining the potential commercial value of the occurrence of adverse events.
Similarly, improved dosing has been patented, for example the use of taxol (U.S. Pat. No. 5,621,001). The new method of using taxol was not, however, based upon a newly discovered adverse event. Rather, the adverse event, neuropathy, was already known to be associated with use of the drug. The inventors conducted clinical trials to decrease the occurrence of the adverse event, but they did not develop a new use of a product based upon the discovery on a new adverse event, furthermore they had contemplated giving a range of doses to ascertain safety of the product when the original compound and method of use were patented. The simple discovery that one dose may be more efficacious or safer than another dose of the same product, does not result in a new use of the product if it had been previously prescribed at such dosages (Classen et al, N. Engl. J. Med. 326(5):281-286 (1992)).
Regulatory agencies do not require new clinical trials to permit a manufacturer to warn of a potential adverse event, even when such adverse events are detected more frequently in certain subgroups. It is considered unethical to perform clinical trials to verify or prove adverse events, since such studies would involve proving one could harm a patient.
Pharmacogenetics and pharmacogenomics are fields dedicated to determining the genetic basis for pharmaceutical phenomenon, such as drug metabolism. For example pharmacogenetics has been utilized to determine why some individuals metabolized a drug faster than another. This approach has been successful when a single enzyme is responsible for the event. Pharmacogenomics is similar to pharmacogenetics, but involves studying the effects of multiple different genes on a characteristic, such as drug metabolism or adverse event. The goal of these fields is to develop genetic tests to individualize pharmaceutical treatment based on a person""s genes. However, these fields do not involve screening databases for new adverse events, rather they start with a defined adverse event, and then attempt to determine the molecular cause of the event. If the pharmacogenetic study leads to a new use, that use involves the use of specific laboratory test, usually a molecular test, in conjunction with the administration of the selected drug. In this situation a prospective clinical trial is needed before regulatory approval, i.e., FDA approval, of the new use. Thus, the new use is not the result of the discovery of the adverse event; it is the product of the clinical trial.
Therefore, prior to the present invention, a need has existed for a system for analyzing adverse event data that is associated with a medical or non-medical product, and for creating useful proprietary adverse event information based on the analyzed adverse event data. The present invention meets this need, and is of particular benefit in connection with products already on the market, because there is potentially extensive pre-existing data for such products that may be analyzed for adverse events.
The invention provides a method, system and article of manufacture by which adverse event information is utilized, for example, to identify new uses for medical or non-medical products or devices, or restrictions that should be applied to their existing uses, or to develop improved packaging or labeling information that should accompany such products or devices. In contrast to the prior art, including the inventor""s earlier filed application U.S. Ser. No. 09/449,178 (now allowed), the current invention involves screening raw adverse event databases to discover new adverse events.
In a preferred embodiment, the method comprises steps, wherein one starts with a linked database that contains adverse events linked to exposure to or use of a device or a product, such as a drug, and further to demographic information of the person, such as age, sex, race, height, weight, tobacco use, alcohol use, preexisting medical conditions, use of medicines etc. The database is screened for adverse events associated with the exposure to a specific product. By using this approach one can find many different adverse events associated with exposure to or use of the product or device. The study can be repeated in a different database, for example, in a database comprising different people. One can determine if the adverse event or use is newly described (i.e., new) by searching recognized databases in the art, such as Medline(copyright).
An additional preferred embodiment of the invention provides a system and method of purifying unprocessed adverse event data, which has little if any utility or value in its raw state, and its subsequent transformation through analysis, tabulation, documentation into proprietary data, which can be commercialized in the form of new uses of a product, and proprietary kits containing the data.
The concept of xe2x80x9cpurificationxe2x80x9d of data is similar to purification of minerals, wherein the unpurified material is of little value, but the purified material may have great commercial value. Prior to the present invention, those in the art, including pharmaceutical companies did not process the raw adverse event data to provide valuable, proprietary, safer uses of drugs or kits to facilitate such uses. The unpurified data was simply published into the public sector.
The present invention utilizes a computerized system for gathering, storing and processing adverse event data associated with medical and non-medical products to create proprietary databases containing useful adverse event information. The adverse event information may be used, for example, to identify new uses or restrictions for medical or non-medical products or devices, or to develop improved packaging information that can accompany medical or non-medical products or devices.
Moreover, the invention contemplates new uses, which do not require adverse events.
In certain preferred embodiments, the system gathers, stores and analyzes vast amounts of adverse event data regarding a product or device, such as from patients being treated by a particular medical product or device. The system can be used to track essentially unlimited product data. The useful adverse event information contained in proprietary databases may include, for example, catalogs of previously known and newly identified adverse events associated with the product or device. The proprietary databases may be subscriber-accessible for direct release to any persons or entities having a need or desire for the information including, without limitation, consumers, manufacturers, research institutions, health care providers, regulatory agencies and attorneys.
The system preferably also has the capability to format the adverse event information for incorporation into licensing contract documents that may be used in negotiations with product manufacturers and/or distributors. The manufacturers and/or distributors, in turn, may use the information to develop and market new uses for existing products. The information may also be used by the manufacturers and/or distributors to provide improved packaging information that can accompany their products to inform users, consumers or medical product or device prescribers of new uses for their medical products or devices. New uses may comprise restrictive uses coupled with directions or warnings not to use the product or device in certain populations or situations where the system according to the invention identifies the risk of adverse events as being increased. Other new uses may include more expansive uses of the product or device. For example, the new use could be coupled with directions to promote more frequent use of the product in certain populations or situations relative to other populations or situations. In either case, a kit can be produced containing the product or device, and improved documentation providing warning, instructions and/or labeling.
Although not limited thereto, the present invention is especially useful in reducing previously unforeseen adverse events caused by medical products including, but not limited to, drugs, vaccines and non-vaccine biologicals, and medical devices. When the medical product is a drug, the product may be proprietary (e.g., protected by patent) or generic.
For non-drug medical products, such as biological products and medical products, as well as non-medical products, similar products having similar characteristics can be adjudged similarly for their adverse event information. For instance, if a red truck and a black truck would be considered the same product if they are equipped with the same or similar fuel tanks, and if their risk of fuel tank explosions is based on the design of the fuel tank.
For devices, whether medical or non-medical, the same principles apply, and the methods, systems and articles of manufacture of invention are provided.
Additional objects, advantages and novel features of the invention will be set forth in part in the description, examples and figures which follow, and in part will become apparent to those skilled in the art on examination of the following, or may be learned by practice of the invention.